The objective of this proposal is to define the importance of nicotine in human cardiovascular disease. The pharmacokinetics and pharcodynamics of nicotine will be examined in healthy male and female volunteers and in patients with coronary heart disease, peripheral vascular disease and essential hypertension. Quantitative relationships between blood nicotine concentrations and sympathetic neural stimulation (heart rate, blood pressure, cutaneous blood flow and plasma catecholamine concentrations) and effects on platelet function will be examined. Circadian variation of nicotine and carboxyhemoglobin concentrations, heart rate and rhythm, skin temperature, plasma and urinary catecholamine excretion and platelet function during daily smoking of low or high nicotine cigarettes or during abstinence will be studied in healthy volunteers and in persons with coronary heart disease, chronic arrhythmias and peripheral vascular disease. In order to better understand the role of cigarette smoking in the progression of hypertensive vascular disease, the effects of nicotine and cigarette smoking on renal hemodynamics, vasopression release and prostaglandin excretion will be studied in healthy volunteers and in individuals with essential hypertension. Results of our studies will clarify the quantitative importance of nicotine in causing acute coronary events as well as in the progression of hypertensive renal vascular disease and may contribute to development of safer cigarettes and future studies of ways to modify tobacco-induced cardiovascular disease.